PXD020639 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The Ig-like domain of Punctin/MADD-4 is the primary determinant for interaction with the ectodomain of neuroligin NLG-1 |
Description | Punctin/MADD-4, a member of the ADAMTSL extracellular matrix protein family, was identified as an anterograde synaptic organizer in the nematode Caenorhabditis elegans. At GABAergic neuromuscular junctions, the short isoform MADD-4B binds the ectodomain of neuroligin NLG-1, itself a postsynaptic organizer of inhibitory synapses. To identify the molecular bases of their partnership, we generated recombinant forms of the two proteins and carried out a comprehensive biochemical and biophysical study of their interaction, complemented by an in vivo localisation study. We show that spontaneous proteolysis of MADD-4B first generates a shorter N-MADD-4B form, which comprises four thrombospondin (TSP) and one Ig-like domains and binds NLG-1. A second processing event eliminates the C-terminal Ig-like domain along with the ability of N-MADD-4B to bind NLG-1. These data identify the Ig-like domain as the primary determinant for N-MADD-4B interaction with NLG-1 in vitro. We further demonstrate in vivo that this Ig-like domain is essential for efficient recruitment of GABAA receptors at GABAergic synapses in C. elegans. The interaction of N-MADD-4B with NLG-1 is also disrupted by heparin, used as a surrogate for the extracellular matrix component, heparan sulphate, and whose high-affinity binding to the Ig-like domain may proceed from surface charge complementarity, as suggested by homology 3D modelling. These data point to N-MADD-4B processing and cell-surface proteoglycan binding as two possible mechanisms that can regulate the interaction between MADD-4B and NLG-1 at GABAergic synapses. |
HostingRepository | PRIDE |
AnnounceDate | 2020-10-12 |
AnnouncementXML | Submission_2020-10-12_03:23:47.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Patrick FOURQUET |
SpeciesList | scientific name: Caenorhabditis elegans; NCBI TaxID: 6239; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-07-29 07:33:18 | ID requested | |
⏵ 1 | 2020-10-12 03:23:48 | announced | |
Publication List
Platsaki S, Zhou X, Pinan-Lucarr, é B, Delauzun V, Tu H, Mansuelle P, Fourquet P, Bourne Y, Bessereau JL, Marchot P, The Ig-like domain of Punctin/MADD-4 is the primary determinant for interaction with the ectodomain of neuroligin NLG-1. J Biol Chem, 295(48):16267-16279(2020) [pubmed] |
Keyword List
submitter keyword: ADAMTS-like, GABA receptor, Punctin/MADD-4, muscle, neuroligin, neuromuscular junction, nicotinic acetylcholine receptor, postsynaptic membrane, protein-protein interaction, synapse |
Contact List
Jean-Paul Borg |
contact affiliation | Centre de Recherche en Cancérologie de Marseille Inserm UMR1068, CNRS UMR7258, Aix-Marseille Université UM105,Institut Paoli-Calmettes 13273 MARSEILLE FRANCE |
contact email | jean-paul.borg@inserm.fr |
lab head | |
Patrick FOURQUET |
contact affiliation | INSERM UMR1068 |
contact email | patrick.fourquet@inserm.fr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020639
- Label: PRIDE project
- Name: The Ig-like domain of Punctin/MADD-4 is the primary determinant for interaction with the ectodomain of neuroligin NLG-1